Prostaglandin endoperoxide synthase, known more commonly as cyclooxygenase (COX), is the key enzyme required for the conversion of arachidonic acid to the biological mediators known as prostanoids, which include prostaglandins, prostacyclin, and thromboxane (Moore and Simmons, 2000). The two COX iso-forms, COX1 and COX2, are expressed in different tissue at varying degrees (Dubois et al., 1998). While COX1 is expressed under basal conditions in almost all tissues and is particularly important to the maintenance of gastric mucosal integrity, renal function, and hemostasis, COX2 is undetectable in most normal tissues (van Ryn et al., 2000). COX2 is highly inducible in cells involved in inflammation and cancer (Rouzer and Marnett, 2009). In addition to the role it plays in inflammation, several lines of research suggest that COX2 is involved in the early stage of tumorigenesis (Yokota et al., 1986; Xie et al., 1991). Notably, COX2 not only continues to express during tumor progress, but the expression of COX2 also indicates an aggressive tumor phenotype that behaves more invasively (Fujita et al., 1998) and thus, a poor prognosis (Sobolewski et al., 2010). COX2 overexpression has been well documented in several human carcinomas including colon (Nasir et al., 2011), stomach (Murata et al., 1999), lung (Hida et al., 1998), breast (Glynn et al., 2010; Singh et al., 2011), head and neck (Chan et al., 1998), bladder (Shimada et al., 2011), and pancreas (Hill et al., 2012). The relationship between cancers and increased COX2 activity provides a rationale for the use of COX2 as a prognostic marker and as a quantifiable indicator of tumor progression and treatment efficacy. Collectively, this approach could be achieved through in vivo imaging of COX2 activity, especially when using a sensitive imaging technique such as positron emission tomography (PET). A number of research initiatives have reported the development of COX2 probes with which to visualize cancer-related inflammation including its use in optical (Uddin et al., 2010) and PET imaging (McCarthy et al., 2002; Prabhakaran et al., 2005; Uddin et al., 2011). However, there is still a need to develop other probes to image COX2.